Dynamics of follicular growth and atresia of large follicles during the ovarian cycle of the guinea pig: fate of the degenerating follicles, a quantitative study.

Background: A quantitative integrated study of healthy ovarian follicles of different sizes and their mitotic activity and of clearly defined atretic stages of involuting large growing follicles at different stages of the guinea pig ovarian cycle is not available in the literature. We considered that such a study would reveal new aspects of ovarian tissue dynamics and provide new information in an organ with a continuous phenotypic transformation of its cellular components.

Methods: Ovaries from guinea pigs were removed on days 1 (opening of the vagina), 3, 6, 9, 13, and 16 of the cycle, and the following were measured in serial sections: (1) total number of healthy follicles falling into categories based on the volume occupied by granulosa cells, (2) total number of atretic follicles falling into clearly defined morphological stages of the degenerative and involutionary process affecting medium to large follicles, and (3) proportion of metaphase-arrested granulosa cells, after colcemid injection, in healthy follicles of different size categories.

Results: Dynamic patterns of follicular growth and degeneration were revealed that permitted the following main conclusions and observations: (1) small to middle-size follicles can reach the maximal category mass of granulosa mass within 6-7 days, and the number of granulosa cells can increase 6-7-fold during this interval, (2) the cohort that gives rise to 2-6 preovulatory follicles and to the large follicles that will undergo atresia during each cycle varied from 68 to 108 follicles, (3) cell death starts in the granulosa cell layers of large follicles even when neighbouring cells maintain a high mitotic activity and it spreads rapidly; dead granulosa cells are cleare by nucleolysis and cytolysis in the absence of blood leucocytes or neovascularization, (4) foci of atresia are observed also in a few preovulatory follicles, (5) antral cavities of follicles with dead granulosa cells in the process of being lysed shrink and are filled within 2-3 days with large fibroblast-like cells arising from phenotypic transformation of inner layers of theca interna, with no evidence of mitotic activity or angiogenesis; the outer layers of theca interna involute, and by progressive atrophy and a process of cell death, minute nodular structures arise with remnants of the ovum and zona pellucida, and (6) a transient wave of degeneration affects a proportion of small and middle-size follicles during the metestrous period. This process does not resemble the morphological phenomenology of follicular involution, which affects only large follicles.

Conclusions: This study contributes to a fuller understanding of the dynamics and time relationships of follicular growth and loss in the guinea pig ovary and provides new morphogenetic information on the atretic process. It would be valuable for the design of experiments on endocrine and paracrine interactions involved in follicular growth and atresia.